Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology Journal Article


Authors: Barbee, M. S.; Ogunniyi, A.; Horvat, T. Z.; Dang, T. O.
Article Title: Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology
Abstract: Objective: To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology. Data Sources: A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX- 010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators’ personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts. Study Selection and Data Extraction: All Englishlanguage clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options. Data Synthesis: Ipilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising. Conclusions: The treatment landscape in oncology is quickly evolving with the advent of ICIs. © 2015, Annals of Pharmacotherapy, All rights Reserved.
Keywords: cancer chemotherapy; treatment response; overall survival; prednisone; drug tolerability; fatigue; cisplatin; placebo; sunitinib; cancer combination chemotherapy; drug efficacy; drug safety; monotherapy; treatment duration; gemcitabine; paclitaxel; cancer patient; neoplasm; carboplatin; dacarbazine; ipilimumab; melanoma; progression free survival; drug eruption; pharmacodynamics; steroid; clinical protocol; kidney failure; practice guideline; oncology; docetaxel; monoclonal antibody; abdominal pain; pneumonia; pruritus; systematic review; arthritis; pazopanib; medline; platinum; colitis; ctla-4; corticosteroid; uvea melanoma; atropine; immunosuppressive agent; pericarditis; antihistaminic agent; pd-1; diphenhydramine; recurrence free survival; steroid therapy; non small cell lung cancer; metastatic melanoma; tumor microenvironment; randomized controlled trial (topic); clinical trial (topic); phase 3 clinical trial (topic); budesonide; conjunctivitis; diphenoxylate; multicenter study (topic); hydroxyzine; data extraction; immune checkpoint inhibitor; nivolumab; blepharitis; eye melanoma; human; priority journal; article; pembrolizumab; drug packaging; sargramostim; scleritis
Journal Title: Annals of Pharmacotherapy
Volume: 49
Issue: 8
ISSN: 1060-0280
Publisher: Sage Publications  
Date Published: 2015-08-01
Start Page: 907
End Page: 937
Language: English
DOI: 10.1177/1060028015586218
PROVIDER: scopus
PUBMED: 25991832
DOI/URL:
Notes: Export Date: 2 November 2015 -- Source: Scopus
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MSK Authors
  1. Thu-Oanh Thi Dang
    11 Dang
  2. Meagan Spencer Barbee
    3 Barbee
  3. Troy Zachery Horvat
    12 Horvat